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Biomedical subjects

Peter G Stock

Publications and source records attributed to Peter G Stock.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation.

The outcome of patients with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) referred for liver transplantation (LT) is unknown. A high frequency of lamivudine-resistant (LAM-R) HBV infection may increase the risk of liver-related death pre-transplantation and prophylaxis failure post-transplantation. We evaluated the association of LAM-R HBV on pre-transplant survival and post-transplant outcomes in 35 consecutive HIV-HBV coinfected patients referred for LT between July 2000 and September 2002. At the time of referral, the median CD4 count was 273/mm, MELD was 14, and LAM-R HBV infection was present in 67%. Among these referred patients, 26% were listed, 29% not listed due to relative/absolute contraindications; 26% not listed as too early for LT; 9% not listed as too sick for LT; and 11% died during transplant evaluation. Of the 9 listed patients, 4 remained listed, 1 died 18 months post-referral, and 4 were transplanted (11% of total) 3 to 40 months after listing. Of 17 evaluated but not listed patients, 5 died (p=0.38 compared to listed group) and all deaths were liver-related. All the HBV-HIV coinfected patients, who were transplanted, are HBsAg negative and have undetectable HBV DNA levels on prophylactic therapy using hepatitis B immune globulin (HBIG) plus lamivudine, with and without tenofovir or adefovir, with median 33.1 months follow-up. Late referral and the presence of LAM-R HBV pre-transplantation are common in referred HIV-HBV patients. In HIV-HBV coinfected patients undergoing LT, HBV recurrence is successfully prevented with combination prophylaxis using HBIG and antivirals.

Adult↗
PubMed2006

Solid organ transplantation is a reality for patients with HIV infection.

Recent policies, guidelines, and laws reflect promising preliminary outcomes among transplant recipients with HIV infection, and ethical analyses suggest that it is not justifiable to deny solid organ transplantation based solely on HIV-infection status. These studies consistently describe stable HIV disease following liver and kidney transplantation. Despite good graft survival, kidney allograft rejection occurs frequently, and serious non-AIDS-defining infections requiring hospitalization are common following antirejection therapy. Profound interactions between immunosuppressants and antiretroviral drugs require careful monitoring, dose adjustment, and highly effective communication between the patient and a multidisciplinary group of health care providers. Despite these scientific and policy advances, many health care providers and patients remain unaware of ongoing progress in this field. The implications are critical, as late referral for liver transplant evaluation increases the pretransplant mortality risk. Because important patient selection and clinical management questions remain, it is critical that ongoing studies are completed quickly.

Anti-HIV Agents↗
PubMed2006

Liver transplantation in HIV-infected recipients.

Although human immunodeficiency virus (HIV)-infected patients are living longer and dying less often from complications related to acquired immunodeficiency syndrome (AIDS), they are experiencing significant morbidity and mortality related to end-stage liver disease. Advances in the management of HIV disease have made it difficult to continue denying transplantation to this population based upon futility arguments alone. Patient and graft survival rates in HIV-infected study subjects appear similar to those in large transplant databases. There are no reports suggesting significant HIV disease progression. There are substantial interactions between immunosuppressants and antiretroviral drugs that require careful monitoring and dose adjustment. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team and the primary HIV care provider. It is critical that HIV clinicians and hepatologists are aware that liver transplantation is an option for HIV-infected patients at many transplant centers as delays in referral result in unnecessary mortality during the pretransplantation evaluation process.

AIDS-Related Opportunistic Infections↗
PubMed2006

Solid organ transplantation: referral, management, and outcomes in HIV-infected patients.

Advances in HIV management make it difficult to deny solid organ transplantation to HIV-infected patients based on futility arguments. Preliminary studies suggest that both patient and graft survival are similar in HIV-negative and HIV-positive transplant recipients. While there has been no significant HIV disease progression, substantial interactions between immunosuppressants and antiretroviral drugs necessitate careful monitoring. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team, the primary HIV care provider, and the patient. Timely referral for transplant evaluation will prevent unnecessary mortality during the pre-transplant evaluation process.

HIV Infections↗
PubMed2005

Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients.

BACKGROUND: With advances in antiretroviral therapy, many human immunodeficiency virus (HIV)-infected individuals are living longer and developing end-stage renal or hepatic disease requiring transplantation. Maintaining the viability of the transplant and suppressing HIV replication requires concomitant use of immunosuppressants (e.g., cyclosporine) and antiretrovirals (e.g., protease inhibitors or nonnucleoside reverse transcriptase inhibitors), which leads to drug interactions. To assist in appropriate clinical management of HIV-infected transplant recipients, the authors describe the pharmacokinetic interactions between cyclosporine and the antiretroviral medications, and required modifications of cyclosporine dosing. METHODS: Eighteen HIV-infected subjects with end-stage kidney or liver disease underwent transplantation. Subjects had pharmacokinetic studies before transplantation and for up to 2 years posttransplantation (at weeks 2-4, 12, 28, 52, and 104). Protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and cyclosporine concentrations were measured by liquid chromatography-mass spectrometry in plasma and whole blood, respectively. RESULTS: Subjects using protease inhibitors and cyclosporine had a threefold increase in cyclosporine area under the curve (4,190+/-2,180-11,900+/-1,600 ng*hr/mL, P<0.01), necessitating an 85% reduction in cyclosporine dose over a 2-year period (1.3+/-1.5-0.2+/-0.0 mg/kg/dose), leading to a progressive increase in oral cyclosporine bioavailability (R=0.92, P<0.02). Subjects on nonnucleoside reverse-transcriptase inhibitors showed minimal interactions with cyclosporine, and subjects on both HIV treatments had intermediate responses. CONCLUSIONS: HIV-infected transplant recipients on protease inhibitors require markedly lower doses of cyclosporine, with continued lowering of the cyclosporine dose over time and ongoing cyclosporine trough monitoring because of progressively increasing cyclosporine bioavailability. Medication changes must be carefully managed to avoid insufficient immunosuppression or toxicity resulting from drug interactions.

Adolescent↗
PubMed2005

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation.

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.

Adult↗
PubMed2005

Current status of kidney and pancreas transplantation in the United States, 1994-2003.

This article reviews the OPTN/SRTR data collected on kidney and pancreas transplantation during 2003 in the context of trends over the past decade. Overall, the transplant community continued to struggle to meet the increasing demand for kidney and pancreas transplantation. The number of new wait-listed kidney registrants under the age of 50 has remained relatively stable since 1994, but the number of new registrants aged 50 to 64 has doubled. However, there was only a 2.3% increase in the total number of kidney transplants performed in 2003. Expanded criteria donor kidneys made up 20% of all recovered kidneys and 16% of all transplants performed, compared with 15% in the prior year. In May 2003, new rules were implemented to promote equity in kidney organ allocation. These changes seem to have improved access for historically disadvantaged groups, though they have reduced the quality of HLA matching. The effects on long-term outcomes have yet to be measured. Although the majority of SPK recipients are white (82%), the percentage of simultaneous kidney-pancreas recipients who are African-American has increased from 9% in 2000 to 16% in 2003. The percentage of Hispanic/Latino recipients increased from 5% to 9% over the same period.

Graft Survival↗
PubMed2005

BKV in simultaneous pancreas-kidney transplant recipients: a leading cause of renal graft loss in first 2 years post-transplant.

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.

Adult↗
PubMed2005

Determinants of transplant surgeons' willingness to provide organs to patients infected with HBV, HCV or HIV.

The common provision of organs to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), but not to those infected with human immunodeficiency virus (HIV), has been attributed to perceived or real differences in transplantation efficacy among these populations. However, other explanations remain possible. We surveyed all active U.S. transplant surgeons to identify determinants of their views of the propriety of transplantation among HBV-, HCV-, and HIV-infected patients. The 347 surgeons (56.1%) returning completed questionnaires believed that HCV- and HIV-infected patients have similar post-transplant survival (p = 0.9), but that both groups fare worse than HBV-infected patients (p < 0.00001 for both comparisons). Most transplant surgeons considered HBV- and HCV-infected patients to be appropriate transplantation candidates (p = 1.0 for this comparison), whereas one-third considered HIV-infected patients to be appropriate candidates (p < 0.00001 when compared with HBV- or HCV-infected patients). That surgeons are generally willing to transplant HCV-infected patients but not HIV-infected patients, and yet believe these groups will have similar post-transplant survival, suggests that survival estimates alone do not explain surgeons' choices. HIV-infected patients should have equal access to organs unless or until evidence emerges that they fare substantially worse than other potential recipients.

Attitude of Health Personnel↗
PubMed2004

Ethical issues in split versus whole liver transplantation.

Technologic advances in split liver transplantation have resulted in an ethical dilemma. Although splitting a liver maximizes the number of patients receiving an organ transplant, it may increase the morbidity and mortality for the individual patient receiving the split liver. This essay explores the ethical issues involved in the allocation of split livers, and proposes general policy guidelines for the allocation of split versus whole liver transplants.

Hepatectomy↗
PubMed2004

Beta-cell replacement for type I diabetes.

The ability to achieve insulin independence with either solid-organ pancreas or islet transplantation has increased the number of patients seeking beta-cell replacement as an alternative to insulin therapy. Despite dramatic improvements in the ability to achieve insulin independence following solid-organ pancreas transplantation, the secondary complications of long-standing diabetes are frequently irreversible by the time surgical intervention is justified based on the risk of this procedure. Pancreatic islet transplantation provides a safer and less invasive alternative for beta-cell replacement that could be justified earlier in the course of diabetes to prevent the development of secondary complications. Recent advances in the technology of islet isolation, as well as the ability to prevent the alloimmune and recurrent autoimmune response following islet transplantation with immunosuppressive regimens that are not toxic to beta cells, have rekindled an interest in this field. Widespread application of islet transplantation will depend on further improvements in selective immunosuppression, development of immunologic tolerance, and finding new sources of beta cells.

Clinical Protocols↗
PubMed2004

Review of transplantation in HIV patients during the HAART era.

Human immunodeficiency virus (HIV) infection was once thought to be a relative or even absolute contraindication to transplantation. With the recent advent of highly active antiretroviral therapy (HAART), those infected with HIV are now living longer and dying from illnesses other than acquired immunodeficiency syndrome (AIDS). Although studies prior to the HAART era suggested poor outcomes might occur with transplantation in those infected with HIV, more recent studies have demonstrated results comparable to those of recipients without HIV infection. A number of issues persist regarding ethics, patient selection, post-operative management, and drug interactions between antiretroviral and immunosuppression agents. In this review, kidney, liver, and heart transplantation in the HIV-positive population were analyzed using data from the Organ Procurement and Transplantation Network/ Scientific Registry of Transplant Recipients.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have historically been excluded from consideration for transplantation out of concern for the effects of immunosuppression on the progression of HIV disease. Improvements in HIV-related morbidity and mortality with the use of highly active antiretroviral therapy (HAART) have prompted a reevaluation of transplantation as a treatment option for HIV-infected patients with end-stage kidney and liver disease. METHODS: Eligible patients met standard transplant criteria. They had undetectable plasma HIV-1 RNA levels (viral load) for 3 months (kidney) or were predicted to achieve viral load suppression posttransplantation if unable to tolerate HAART (liver); a CD4+ T-cell count of more than 200 cells/microL (kidney) or more than 100 cells/microL (liver) for 6 months; and no history of opportunistic infections and neoplasm. Standard immunosuppression included prednisone, mycophenolate mofetil (CellCept, Roche Pharmaceuticals, Basel, Switzerland), and cyclosporine (Neoral, Novartis, East Hanover, NJ). RESULTS: Fourteen patients received transplants (10 kidney transplants, mean follow-up 480 days; four liver transplants, mean follow-up 380 days). All of the kidney transplant recipients (100%) are alive and with functioning grafts, and three of four liver transplant patients (75%) are alive and well with functioning grafts (all liver transplant patients with normal liver function tests). The one death occurred 445 days posttransplantation in a liver recipient coinfected with hepatitis C virus, who died as the result of its rapid reoccurrence. Rejection occurred in 5 of 10 kidney transplant recipients but did not occur in any of the four liver transplant recipients. HIV viral loads have remained undetectable in all patients maintained with HAART. CD4 counts have remained stable in patients not treated for rejection. Patients receiving protease inhibitors require 25% of the dose of cyclosporine compared with patients receiving nonnucleoside reverse transcriptase inhibitors. CONCLUSIONS: There has been no evidence of significant HIV progression and no adverse effect of HIV on allograft function. Rejection is a concern in kidney transplant recipients, as is the possible poor outcome in hepatitis C virus-coinfected liver transplant recipients. Preliminary data are encouraging and indicate that transplantation should be a treatment option for individuals with well-controlled HIV disease.

Adult↗
PubMed2003

The year in review--ATC 2002.

Strategies for dealing with the exponential growth of the waiting lists for solid organ transplants were the hottest clinical topics in 2002, and dominated the abstracts presented at ATC 2002. Other clinical topics that were prominent in the 2002 literature and received the highest scores at ATC 2002 included: the development of immunosuppressive regimens minimizing calcineurin inhibitors and eliminating steroids; the increasing frequency and severity of hepatitis C recurrence following transplantation; the safety and efficacy of solid organ transplantation in HIV-positive recipients; the induction of tolerance with donor stem cell infusion and recipient preconditioning; the increasing incidence of BK virus; and beta-cell replacement for the treatment of diabetes mellitus.

BK Virus↗
PubMed2003

Management of lymphoceles after renal transplantation: laparoscopic versus open drainage.

PURPOSE: Laparoscopic surgery has become widely accepted for the treatment of lymphoceles following kidney transplantation. In this single center study we retrospectively reviewed our results of the surgical management of post-transplant lymphoceles, assessing indication and outcome of laparoscopic versus open drainage. MATERIALS AND METHODS: The records of 60 patients who underwent surgical treatment for a symptomatic lymphocele following kidney transplantation or combined kidney/pancreas transplantation were retrospectively reviewed. RESULTS: Between 1995 and 2002, 1,836 patients received a kidney transplant at the University of California San Francisco. In 60 patients (3.3%) a symptomatic lymphocele developed and either laparoscopic (20) or open drainage (40) was completed. The conversion rate from laparoscopic to open drainage was 16.5%. The most common indications for open lymphocele drainage were noninfectious wound complications (13 patients) and a high risk of vessel or ureter injury (8) due to proximity of the lymphocele to hilar structures. Additional surgery on the graft was required in 5 patients. Intraoperative blood loss was significantly lower in the laparoscopy group. Median hospital stay was 1 day in the laparoscopy group versus 4 days in the open drainage group. No perioperative complications were observed in either group. After a median followup of 38 months, 2 patients in each treatment group had a symptomatic recurrence. CONCLUSIONS: Although both surgical approaches are safe and effective, laparoscopic drainage should remain the method of choice for the treatment of post-transplant lymphocele. However, open drainage should be performed in patients with wound complications and in those with a small lymphocele adjacent to vital renal structures.

Adult↗
PubMed2002

Successful long-term outcomes using pediatric en bloc kidneys for transplantation.

GOAL: The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. MATERIALS AND METHODS: A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. FINDINGS: Fifty-seven adult recipients with at least a 1-year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)- or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5- and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0+/-0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/MMF had rejection. Nine patients (16%) had surgical complications. CONCLUSION: Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients.

Age Factors↗